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A Tuberculosis Molecular Bacterial Load Assay TB-MBLA
Published on: April 30, 2020
Biomarkers for discrimination between latent tuberculosis infection and active tuberculosis disease
Eun-Jeong Won1, Jung-Ho Choi1, Young-Nan Cho2
1Department of Laboratory Medicine, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Insights
Multiplex cytokine responses can differentiate Mycobacterium tuberculosis (Mtb) infection states. Combinations of biomarkers accurately predict active TB, latent TB infection, and healthy controls.
Area of Science:
- Immunology
- Infectious Diseases
- Biomarker Discovery
Background:
- Accurate differentiation of Mycobacterium tuberculosis (Mtb) infection states is crucial for effective disease management.
- Multiplex cytokine profiling offers a potential avenue for non-invasive diagnostics.
Purpose of the Study:
- To investigate whether combinations of multiplex cytokine responses can distinguish between active tuberculosis (TB), latent TB infection (LTBI), and healthy controls (HCs).
- To identify specific cytokine biomarkers indicative of different Mtb infection states.
Main Methods:
- Cytokine levels were measured using Luminex assay in supernatants from QuantiFERON® Gold In-Tube (QFT) assays.
- Samples were collected from active TB patients, LTBI subjects, and HCs.
- Statistical analyses were performed to identify significant differences in cytokine levels and ratios between groups.
Main Results:
- Eight Mtb antigen-specific biomarkers differed significantly between Mtb-infected individuals and HCs.
- Specific Mtb-specific and unstimulated biomarkers, along with an IL-2/IFN-γ ratio, differentiated active TB from LTBI.
- Combinations of three to six cytokine biomarkers demonstrated high accuracy in predicting Mtb infection states, including active TB and LTBI.
Conclusions:
- Combinations of whole blood Mtb antigen-dependent cytokines can serve as effective biomarkers for determining TB disease states.
- Vascular Endothelial Growth Factor (VEGF) emerged as a key biomarker for active TB, independent of stimulation.
Objective:
We aimed to determine whether combinations of multiplex cytokine responses could differentiate Mycobacterium tuberculosis (Mtb) infection states.
Methods:
Mtb-specific antigen-induced and unstimulated cytokines were measured by Luminex assay in supernatants of QuantiFERON® Gold In-Tube assay (QFT) in 48 active pulmonary TB patients (TB), 15 latent TB infection subjects (LTBI), and 13 healthy controls (HCs).
Results:
Among the 29 cytokines, eight Mtb antigen-specific biomarkers (GM-CSF, IFN-γ, IL-1RA, IL-2, IL-3, IL-13, IP-10, and MIP-1β) in the Mtb-infected group were significantly different from those of the HCs. Five Mtb-specific biomarkers (EGF, GM-CSF, IL-5, IL-10, and VEGF), two unstimulated biomarkers (TNF-α[Nil] and VEGF[Nil]), and one Mtb-specific biomarker ratio (IL-2/IFN-γ) showed significant differences between active TB and LTBI. Three unstimulated biomarkers (IL-8[Nil], IL-13[Nil], and VEGF[Nil]) and 5 Mtb-specific biomarkers (IFN-γ, IL-2, IL-3, IP-10, and VEGF) were significantly different between active TB and non-active TB groups. Combinations of three cytokine biomarkers resulted in the accurate prediction of 92.1-93.7% of Mtb-infected cases and 92.3-100% of HCs, respectively. Moreover, combinations of five biomarkers accurately predicted 90.9-100% of active TB cases and 80-100% of LTBI subjects, respectively. In discriminating between active TB and non-active TB regardless of QFT results, combinations of six biomarkers predicted 79.2-95.8% of active TB cases and 67.9-89.3% of non-active TB subjects.
Conclusions:
Taken together, our data suggest that combinations of whole blood Mtb antigen-dependent cytokines could serve as biomarkers to determine TB disease states. Especially, VEGF is highlighted as a key biomarker for reflecting active TB, irrespective of stimulation.
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